KEGG   PATHWAY: mcc04657
Entry
mcc04657                    Pathway                                
Name
IL-17 signaling pathway - Macaca mulatta (rhesus monkey)
Description
The interleukin 17 (IL-17) family, a subset of cytokines consisting of IL-17A-F, plays crucial roles in both acute and chronic inflammatory responses. IL-17A, the hallmark cytokine of the newly defined T helper 17 (TH17) cell subset, has important roles in protecting the host against extracellular pathogens, but also promotes inflammatory pathology in autoimmune disease, whereas IL-17F is mainly involved in mucosal host defense mechanisms. IL-17E (IL-25) is an amplifier of Th2 immune responses. IL-17C has biological functions similar to those of IL-17A. The functions of IL-17B and IL-17D remain largely elusive. The IL-17 family signals via their correspondent receptors and activates downstream pathways that include NF-kappaB, MAPKs and C/EBPs to induce the expression of antimicrobial peptides, cytokines and chemokines. The receptor proximal adaptor Act1 (an NF-kappaB activator 1) is considered as the master mediator in IL-17A signaling. It is likely that Act1 is a common signal adaptor also shared by other members mediated signalings in this family.
Class
Organismal Systems; Immune system
Pathway map
mcc04657  IL-17 signaling pathway
mcc04657

Other DBs
GO: 0097400
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
713943  IL25; interleukin-25 isoform X2 [KO:K05493]
709005  IL17RA; interleukin-17 receptor A [KO:K05164]
693671  IL17RB; interleukin-17 receptor B isoform X1 [KO:K05165]
114675338  LOW QUALITY PROTEIN: interleukin-17 receptor B-like [KO:K05165]
698160  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
708606  FADD; FAS-associated death domain protein [KO:K02373]
694473  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
702781  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
697530  TRAF3IP2; adapter protein CIKS [KO:K21124]
716907  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
710324  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
715919  RELA; transcription factor p65 isoform X1 [KO:K04735]
702077  FOS; proto-oncogene c-Fos [KO:K04379]
715896  FOSB; protein fosB isoform X1 [KO:K09029]
716452  JUN; transcription factor AP-1 [KO:K04448]
720182  JUND; transcription factor jun-D [KO:K04449]
106993191  FOSL1; fos-related antigen 1 [KO:K04502]
574281  IL4; interleukin-4 precursor [KO:K05430]
710622  IL5; interleukin-5 precursor [KO:K05428]
574325  IL13; interleukin-13 precursor [KO:K05435]
574180  CCL17; C-C motif chemokine 17 precursor [KO:K21083]
574218  CCL11; eotaxin precursor [KO:K16597]
708123  IL17A; interleukin-17A [KO:K05489]
708220  IL17F; interleukin-17F precursor [KO:K05494]
699223  IL17RC; interleukin-17 receptor C isoform X1 [KO:K05166]
693961  TRAF3; TNF receptor-associated factor 3 isoform X1 [KO:K03174]
699821  ANAPC5; anaphase-promoting complex subunit 5 isoform X1 [KO:K03352]
704130  TNFAIP3; tumor necrosis factor alpha-induced protein 3 [KO:K11859] [EC:3.4.19.12]
702293  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
708431  HSP90AA1; heat shock protein 90kDa alpha (cytosolic), class A member 1 [KO:K04079]
699568  HSP90B1; endoplasmin precursor [KO:K09487]
717427  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
696875  TAB2; TGF-beta-activated kinase 1 and MAP3K7-binding protein 2 [KO:K04404]
707630  TAB3; TGF-beta-activated kinase 1 and MAP3K7-binding protein 3 isoform X1 [KO:K12793]
703101  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
701237  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
709511  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467] [EC:2.7.11.10]
704683  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
695335  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
715745  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
715794  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
718976  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
719085  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
699736  MAPK10; mitogen-activated protein kinase 10 isoform 1 [KO:K04440] [EC:2.7.11.24]
711115  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
715782  MAPK9; mitogen-activated protein kinase 9 isoform X2 [KO:K04440] [EC:2.7.11.24]
708938  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
698569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
700969  MAPK4; mitogen-activated protein kinase 4 [KO:K06855] [EC:2.7.11.24]
694998  MAPK6; mitogen-activated protein kinase 6 [KO:K06855] [EC:2.7.11.24]
702837  MAPK7; mitogen-activated protein kinase 7 isoform X4 [KO:K04464] [EC:2.7.11.24]
100428659  MAPK15; mitogen-activated protein kinase 15 isoform X2 [KO:K19603] [EC:2.7.11.24]
713191  CEBPB; CCAAT/enhancer-binding protein beta [KO:K10048]
716364  TRAF4; TNF receptor-associated factor 4 isoform X1 [KO:K09848]
695607  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
716923  USP25; ubiquitin carboxyl-terminal hydrolase 25 isoform X7 [KO:K11849] [EC:3.4.19.12]
711879  TRAF5; TNF receptor-associated factor 5 isoform X1 [KO:K09849]
708391  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
713958  SRSF1; serine/arginine-rich splicing factor 1 [KO:K12890]
705806  ELAVL1; ELAV-like protein 1 [KO:K13088]
713114  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
574222  CXCL1; growth-regulated alpha protein precursor [KO:K05505]
703390  growth-regulated alpha protein-like [KO:K05505]
702067  uncharacterized protein LOC702067 [KO:K05505]
100424064  growth-regulated alpha protein-like [KO:K05505]
574223  CXCL3; C-X-C motif chemokine 3 precursor [KO:K05505]
701946  C-X-C motif chemokine 5 [KO:K05506]
703222  C-X-C motif chemokine 5 [KO:K05506]
704133  CXCL6; C-X-C motif chemokine 6 [KO:K05506]
613028  CXCL8; interleukin-8 precursor [KO:K10030]
574243  CXCL10; C-X-C motif chemokine 10 precursor [KO:K12671]
574138  CCL2; C-C motif chemokine 2 precursor [KO:K14624]
714751  CCL7; C-C motif chemokine 7 [KO:K05509]
574182  CCL20; C-C motif chemokine 20 precursor [KO:K14625]
705819  IL6; interleukin-6 precursor [KO:K05405]
715467  TNF; tumor necrosis factor [KO:K03156]
716671  PTGS2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
698961  CSF3; granulocyte colony-stimulating factor [KO:K05423]
574371  CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
100169969  DEFB4; beta-defensin 4A precursor [KO:K21100]
114675435  beta-defensin 4A-like [KO:K21100]
114675439  beta-defensin 4A-like [KO:K21100]
114676064  beta-defensin 4A-like [KO:K21100]
114680396  beta-defensin 4A-like [KO:K21100]
720912  MUC5AC; mucin-5AC [KO:K13908]
100429390  MUC5B; mucin-5B [KO:K13908]
713189  protein S100-A7 [KO:K21126]
714943  protein S100-A7 [KO:K21126]
714740  S100A8; protein S100-A8 [KO:K21127]
714690  S100A9; protein S100-A9 [KO:K21128]
697208  LCN2; neutrophil gelatinase-associated lipocalin [KO:K21129]
703653  MMP1; interstitial collagenase [KO:K01388] [EC:3.4.24.7]
703762  MMP3; stromelysin-1 [KO:K01394] [EC:3.4.24.17]
708084  MMP9; matrix metalloproteinase-9 precursor [KO:K01403] [EC:3.4.24.35]
703980  MMP13; collagenase 3 [KO:K07994] [EC:3.4.24.-]
710618  IL17C; interleukin-17C [KO:K05491]
698972  IL17RE; interleukin-17 receptor E isoform X4 [KO:K05168]
704701  IL1B; interleukin-1 beta precursor [KO:K04519]
574282  IFNG; interferon gamma precursor [KO:K04687]
710679  IL17B; interleukin-17B [KO:K05490]
721163  IL17D; interleukin-17D isoform X1 [KO:K05492]
Reference
PMID:23917206
  Authors
Song X, Qian Y
  Title
IL-17 family cytokines mediated signaling in the pathogenesis of inflammatory diseases.
  Journal
Cell Signal 25:2335-47 (2013)
DOI:10.1016/j.cellsig.2013.07.021
Reference
PMID:23557798
  Authors
Song X, Qian Y
  Title
The activation and regulation of IL-17 receptor mediated signaling.
  Journal
Cytokine 62:175-82 (2013)
DOI:10.1016/j.cyto.2013.03.014
Reference
PMID:24011563
  Authors
Gu C, Wu L, Li X
  Title
IL-17 family: cytokines, receptors and signaling.
  Journal
Cytokine 64:477-85 (2013)
DOI:10.1016/j.cyto.2013.07.022
Reference
PMID:25145755
  Authors
Gaffen SL, Jain R, Garg AV, Cua DJ
  Title
The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing.
  Journal
Nat Rev Immunol 14:585-600 (2014)
DOI:10.1038/nri3707
Reference
PMID:21349428
  Authors
Iwakura Y, Ishigame H, Saijo S, Nakae S
  Title
Functional specialization of interleukin-17 family members.
  Journal
Immunity 34:149-62 (2011)
DOI:10.1016/j.immuni.2011.02.012
Reference
PMID:20514051
  Authors
Qian Y, Kang Z, Liu C, Li X
  Title
IL-17 signaling in host defense and inflammatory diseases.
  Journal
Cell Mol Immunol 7:328-33 (2010)
DOI:10.1038/cmi.2010.27
Reference
PMID:22324470
  Authors
Zhu S, Qian Y
  Title
IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential.
  Journal
Clin Sci (Lond) 122:487-511 (2012)
DOI:10.1042/CS20110496
Reference
PMID:26252407
  Authors
Zenobia C, Hajishengallis G
  Title
Basic biology and role of interleukin-17 in immunity and inflammation.
  Journal
Periodontol 2000 69:142-59 (2015)
DOI:10.1111/prd.12083
Reference
PMID:21074482
  Authors
Reynolds JM, Angkasekwinai P, Dong C
  Title
IL-17 family member cytokines: regulation and function in innate immunity.
  Journal
Cytokine Growth Factor Rev 21:413-23 (2010)
DOI:10.1016/j.cytogfr.2010.10.002
Reference
PMID:21852080
  Authors
Gaffen SL
  Title
Recent advances in the IL-17 cytokine family.
  Journal
Curr Opin Immunol 23:613-9 (2011)
DOI:10.1016/j.coi.2011.07.006
Reference
PMID:18701318
  Authors
Gaffen SL
  Title
An overview of IL-17 function and signaling.
  Journal
Cytokine 43:402-7 (2008)
DOI:10.1016/j.cyto.2008.07.017
Reference
PMID:21155836
  Authors
Hu Y, Shen F, Crellin NK, Ouyang W
  Title
The IL-17 pathway as a major therapeutic target in autoimmune diseases.
  Journal
Ann N Y Acad Sci 1217:60-76 (2011)
DOI:10.1111/j.1749-6632.2010.05825.x
Reference
PMID:20383173
  Authors
Xu S, Cao X
  Title
Interleukin-17 and its expanding biological functions.
  Journal
Cell Mol Immunol 7:164-74 (2010)
DOI:10.1038/cmi.2010.21
Reference
PMID:20177959
  Authors
Pappu R, Ramirez-Carrozzi V, Ota N, Ouyang W, Hu Y
  Title
The IL-17 family cytokines in immunity and disease.
  Journal
J Clin Immunol 30:185-95 (2010)
DOI:10.1007/s10875-010-9369-6
Reference
PMID:19575028
  Authors
Gaffen SL
  Title
Structure and signalling in the IL-17 receptor family.
  Journal
Nat Rev Immunol 9:556-67 (2009)
DOI:10.1038/nri2586
Reference
PMID:18178098
  Authors
Shen F, Gaffen SL
  Title
Structure-function relationships in the IL-17 receptor: implications for signal transduction and therapy.
  Journal
Cytokine 41:92-104 (2008)
DOI:10.1016/j.cyto.2007.11.013
Reference
PMID:23116200
  Authors
Doyle MS, Collins ES, FitzGerald OM, Pennington SR
  Title
New insight into the functions of the interleukin-17 receptor adaptor protein Act1 in psoriatic arthritis.
  Journal
Arthritis Res Ther 14:226 (2012)
DOI:10.1186/ar4071
Reference
PMID:17027518
  Authors
Gaffen SL, Kramer JM, Yu JJ, Shen F
  Title
The IL-17 cytokine family.
  Journal
Vitam Horm 74:255-82 (2006)
DOI:10.1016/S0083-6729(06)74010-9
Reference
PMID:21130872
  Authors
Chang SH, Dong C
  Title
Signaling of interleukin-17 family cytokines in immunity and inflammation.
  Journal
Cell Signal 23:1069-75 (2011)
DOI:10.1016/j.cellsig.2010.11.022
Reference
PMID:17921324
  Authors
Cortez DM, Feldman MD, Mummidi S, Valente AJ, Steffensen B, Vincenti M, Barnes JL, Chandrasekar B
  Title
IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2-dependent C/EBP-beta , NF-kappaB, and AP-1 activation.
  Journal
Am J Physiol Heart Circ Physiol 293:H3356-65 (2007)
DOI:10.1152/ajpheart.00928.2007
Reference
PMID:22851696
  Authors
Qu F, Gao H, Zhu S, Shi P, Zhang Y, Liu Y, Jallal B, Yao Y, Shi Y, Qian Y
  Title
TRAF6-dependent Act1 phosphorylation by the IkappaB kinase-related kinases suppresses interleukin-17-induced NF-kappaB activation.
  Journal
Mol Cell Biol 32:3925-37 (2012)
DOI:10.1128/MCB.00268-12
Reference
PMID:17177681
  Authors
Sharkhuu T, Matthaei KI, Forbes E, Mahalingam S, Hogan SP, Hansbro PM, Foster PS
  Title
Mechanism of interleukin-25 (IL-17E)-induced pulmonary inflammation and airways hyper-reactivity.
  Journal
Clin Exp Allergy 36:1575-83 (2006)
DOI:10.1111/j.1365-2222.2006.02595.x
Related
pathway
mcc04010  MAPK signaling pathway
mcc04060  Cytokine-cytokine receptor interaction
mcc04064  NF-kappa B signaling pathway
mcc04210  Apoptosis
mcc04659  Th17 cell differentiation
KO pathway
ko04657   
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